Endocrine Abstracts

Many cases of hypertension are associated with inappropriately high levels of aldosterone secretion and it has been proposed that microRNAs play a role in this dysregulation. Previously, we showed that microRNAs expressed within the adrenal cortex significantly repress aldosterone production. Furthermore, stimulation of aldosterone secretion by three different means in the H295R cell line – the most commonly-used in vitro model of the human adrenal cortex – ...

Inappropriately high secretion of aldosterone can lead to hypertension and its various cardiovascular consequences. We previously showed that microRNA (miRNA) plays a significant role in the regulation of aldosterone biosynthesis. In this study we measured miRNA levels in H295R cells, the most commonly-used human adrenocortical cell line, and investigated how these change in response to the stimulation of aldosterone biosynthesis.H295R cells (n=...

Peripheral insulin resistance is a major defect associated with glucose intolerance and type two diabetes. Yet the mechanism(s) responsible for this defect remain to be determined. Inositol pyrophosphate (IP7) is formed via the enzyme IP6K1 from IP6. The inhibition of Akt, and the potential decrease in insulin signalling, through the binding of IP7 to the Akt PH domain represents an exciting research area.Firstly, we will characterise this mechanism in h...

The CYP11B1 and CYP11B2 genes encode the enzymes responsible, respectively, for the terminal stages of cortisol and aldosterone biosynthesis, and have been implicated in the development of essential hypertension. Previously, we investigated the role of microRNAs in the regulation of these genes and showed in vitro that levels of the adrenally-expressed microRNA-24 (miR-24) inversely correlate with those of CYP11B1 and CYP11B2 mRNA, ...

The final reaction for cortisol production in the adrenal gland is catalysed by the 11β-hydroxylase enzyme, encoded by the CYP11B1 gene. Variants in this gene have been associated with alterations in cortisol levels, which increase blood pressure. This gene is traditionally thought to consist of 9 exons. However, recent evidence has predicted the existence of at least one alternatively spliced form.The presence of novel CYP11B1 mRN...

Annexin A1 (AnxA1), an endogenous glucocorticoid regulated protein, is a pivotal homeostatic regulator of the magnitude of the inflammatory response. We have previously demonstrated that plasma AnxA1 protein is significantly inversely correlated with waist to hip ratio (P=0.017). Given that low-level systemic inflammation is seen in metabolic syndrome-associated chronic pathologies, here, we investigate if AnxA1 is also involved in the regulation of adipose tissue infla...

Essential hypertension is known to have a large genetic component. Variation in the CYP11B2 gene, which encodes the aldosterone synthase enzyme, is associated with excess aldosterone production and hypertension but the causative mechanism remains elusive. miRNAs are a class of post-transcriptional regulatory molecules, implicated in cardiovascular disease, development and tumourogenesis. They act by targeting the 3′ untranslated region (UTR) of mRNAs, inhibiting t...

The escalating public health problem represented by obesity has spurred multidisciplinary research into adipose tissue and importantly, the molecular biology of the adipocyte. Recent studies suggest that obesity related metabolic disorders are characterised by chronic mild inflammation as a result of adipocytokine production from fat tissue leading to dysregulation in the pro/anti-inflammatory systemic balance. Adipokines and pro-inflammatory markers are implicated in insulin ...

The CYP11B1 and CYP11B2 genes encode 11β-hydroxylase and aldosterone synthase, which catalyse the production of cortisol and aldosterone, respectively, and have been implicated in the development of hypertension. For this study, we wished to investigate the role of microRNAs (miRNAs), a novel class of post-transcriptional gene regulators. To that end, we generated a profile of human adrenal miRNAs to study, and then investigated the action of one adrenal miR...

Background: The CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) genes are found in close proximity on human chromosome 8 and are highly polymorphic, enabling the definition of two common haplotypes. Haplotype1 includes the -344T and the Intron2 conversion polymorphisms in CYP11B2 and also the -1889T, -1859G polymorphisms in the regulatory region of CYP11B1. We and others have shown that these associate with increased aldosterone pr...